Immunopathologic mechanisms relating in either a direct or indirect manner to basic cartilagenous constituents are to be studied as to their potential role in the causation and/or perpetuation or articular inflammation and cartilage degradation. Proteoglycans are to be derived from normal and pathologic articular cartilage by dissociative and "mild" disruptive measures in conjunction with cesium gradient ultracentrifugation and characterized both immunologically and by polyacrilamide disc gel electrophoresis. Chondrocytes, isolated by collagenase digestion, are to be maintained in an undifferentiated form in monolayer culture. The effect of proteoglycans upon B-cell immunoglobulin synthesis and T- and B- cell mitogenic responsiveness will be evaluated as well as their effect on bacterial phagocytosis and killing. Circulating, synovial fluid and synovial membrane eluted antibody to such antigens will be determined by immunodiffusion, hemagglutination, immunofluorescence and radioimmunoassay techniques. Cell mediated immunity to proteoglycans is to be assessed by blastogenesis and macrophage migration inhibitory and lymphotoxin factor assays whereas chondrocyte sensitization will be detected employing a two cell system using appropriate skin fibroblast HLA controls. Our current investigations pertaining to the capacity of factors liberated by a mitogenically induced lymphocyte/monocyte interaction capable of directly inducing degradation of cartilage proteoglycans as well as modification of chondrocytes synthetic capacity require extension. In addition, experimental animal models of inflammatory and degenerative joint disease will be utilized to study sequential immunopathologic events as relates to cartilage moieties.